Artmether and Lumefantrine: Antimalarial agents - Gafacom (For health. For knowledge)

Artmether and Lumefantrine: Antimalarial agents


Antimalarial agents

Pharmacological action

Artmether with Lumefantrine tablet, a fixed ratio of 1:6 parts of artmether and Lumefantrine, respectively is an antimalarial agent. Artmether is rapidly metabolized into an active metabolite dihydroartemisinin (DHA). The anti-malarial activity of artmether and ADH has been attributed to endoperoxide moiety. The exact mechanism by which Lumefantrine exerts its anti-malaria effect is not well defined. Available data suggest Lumefantrine inhibits the formation of β-hematin by forming a complex with hemin. Both Artmether and Lumefantrine were shown to inhibit nucleic acid and protein synthesis.
Artmether with Lumefantrine tablet, a fixed ratio of 1:6
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Pharmacokinetic

Absorption: Food enhances the absorption of both artmether and lumefantrine. Artmether is absorbed with peak plasma concentrations reached about 2 hours after dosing. Absorption of Lumefantrine, a highly lipophilic compound, starts after a lag-time of up to 2 hours, with peak plasmaconcentrations about 6 to 8 hours after administration
Distribution: Artmether and Lumefantrine are both highly bound to human serum proteins in vitro (95.4% and 99.7% respectively). Dihydroartemisinin is also bound to human serum proteins (47% to 76%)

Metabolism: The metabolism of Artmether is catalyzed predominantly by CYP3A/5. Dihydroartemisinin (DHA) is an active metabolite of artmether. The metabolism of artmether is also catalyzed to a lesser extent by CYP2B6, CYP2C9 and CYP2C19. Lumefantrine is metabolized mainly by CYP3A4 to desbutyl-lumefantrine. This systemic exposure to the metabolite desbutyl-lumefantrine is less than 1% of the exposure to the parent compound.
Excretion: Artmether and DHA are cleared from plasma with an elimination half-life of about 2 hours. Lumefantrine is eliminated more slowly, with a terminal half-life of 3-6 days in healthy volunteers and in patients with falciparum malaria





Indications

Artmether with Lumefantrine tablet is indicated for treatment of acute, uncomplicated malaria infections due to Plasmodium falciparum including malaria acquired in areas where chloroquine resistance has been reported.

Contraindications

Hypersensitivity to artmether, lumefantrine or any ingredient in the formulation.

Pregnancy
Pregnancy category C: The efficacy of this tablet in the treatment of acute, uncomplicated malaria in pregnant women has not been established. It should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus.

Lactation
It is not known whether artmether or lumefantrine is excreted in human milk. Caution should be exercised when artmether with lumefantrine tablet administered to a nursing woman. Animal data suggest both artmether and Lumefantrine are excreted into breast milk. The benefits of breastfeeding to mother and infants should be weighed against potential risk from infant exposure to artmether and lumefantrine through breast millk.

Pediatric use
The safety and effectiveness of armether with lumefantrine tablet have been established for the treatment of acute, complicated malaria in children 2 months of age and older with a body weight of 5kg and greater.

Hepatic and renal impairment

No specific pharmacokinetic studies have been performed in patients with either hepatic or renal impairment. No dosage adjustment is necessary in patients with mild to moderate hepatic impairment and renal impairment.



Artmether and Lumefantrine: Antimalarial agents Artmether and Lumefantrine: Antimalarial agents Reviewed by gafacom on March 13, 2020 Rating: 5

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